Oxacillin

Intravenous administration provides peak serum levels approximately 5 minutes after the injection is completed. Slow I.V administration of 500 mg gives a peak serum level of 43 mcg/mL after 5 minutes with a half-life of 20 to 30 minutes.

Oxacillin sodium, with normal doses, has insignificant concentrations in the cerebrospinal and ascitic fluids. It is found in therapeutic concentrations in the pleural, bile, and amniotic fluids.

Oxacillin Sodium is rapidly excreted as unchanged drug in the urine by glomerular filtration and active tubular secretion. The elimination half-life for oxacillin is about 0.5 hours. Nonrenal elimination includes hepatic inactivation and excretion in bile.

Oxacillin sodium binds to serum protein, mainly albumin. The degree of protein binding reported varies with the method of study and the investigator, but generally has been found to be 94.2 ± 2.1%.

Probenecid blocks the renal tubular secretion of penicillins. Therefore, the concurrent administration of probenecid prolongs the elimination of oxacillin and, consequently, increases the serum concentration.

Intramuscular injections give peak serum levels 30 minutes after injection. A 250 mg dose gives a level of 5.3 mcg/mL while a 500 mg dose peaks at 10.9 mcg/mL. Intravenous injection gives a peak about 5 minutes after the injection is completed. Slow IV dosing with 500 mg gives a 5 minute peak of 43 mcg/mL with a half-life of 20 to 30 minutes.

When available, the clinical microbiology laboratory should provide of

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method^1,2(broth and/or agar). The MIC values should be interpreted according to the criteria in Table 1.

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized method.^2,3.It has been determined that the most accurate method to test the susceptibility of microorganisms to penicillinase resistant penicillins, including oxacillin, by disk diffusion is achieved using disks impregnated with 30 mcg cefoxitin. Interpretation involves correlation of the diameter obtained with the cefoxitin disk test with the MIC for oxacillin². Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 microgram cefoxitin disk should be interpreted according to the following criteria in Table 1.

S=susceptible, I=intermediate, R-resistant

• ^aIn most staphylococcal isolates, oxacillin resistance is mediated by mecA, encoding the penicillin binding protein 2a (PBP2a, also called PBP2’). Isolates that test positive for mecA or PBP2a should be reported as oxacillin resistant.”
• ^2bCefoxitin is used as a surrogate for oxacillin; report oxacillin susceptible or resistant based on the cefoxitin result.
• ^2cIf both cefoxitin and oxacillin are tested against
  S. aureus
  or
  S. lugdenensis
  , and either result is resistant, the organism should be reported as oxacillin resistant.
• ^2dOxacillin MIC interpretive criteria may overcall resistance for some coagulase-negative staphylococci (CoNS), because some non-
  S. epidermidis
  strains for which the oxacillin MICs are 0.5 to 2 mcg/ml lack
  mecA
  . For serious infections with CoNS other than
  S. epidermidis
  , testing for
  mecA
  or for PBP 2a or with cefoxitin disk diffusion

A report of “Susceptible” indicates that the antimicrobial is likely to inhibit the growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. A report of “Intermediate” indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test.^1,2,3Standard oxacillin powder should provide the following range of MIC values 1 noted in Table 2. For the diffusion technique using the 30 mcg cefoxitin disk, the criteria in Table 2 should be achieved.

ATCC=American Type Culture Collection

^aDespite the lack of reliable disk diffusion interpretive criteria for

^bDeterioration of oxacillin disk content is best assessed with QC organisms

Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin. The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015 and 0.04 percent. Anaphylactic shock resulting in death has occurred in approximately 0.002 percent of the patients treated.

When oxacillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, oxacillin should be discontinued and appropriate therapy instituted.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against

Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin. The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015 and 0.04 percent. Anaphylactic shock resulting in death has occurred in approximately 0.002 percent of the patients treated.

When oxacillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, oxacillin should be discontinued and appropriate therapy instituted.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against